title: Quinolino-benzo-[5, 6]-dihydroisoquindolium compounds derived from berberine: a new class of highly selective ligands for G-quadruplex DNA in c-myc oncogene.
abstract: A series of quinolino-benzo-[5, 6]-dihydroisoquindolium compounds (3a, 3f, 3g, and 3j) derived from alkaloid berberine were designed and synthesized as novel G-quadruplex ligands. Subsequent biophysical and biochemical evaluation demonstrated that the addition of pyridine ring and amino group into berberine improved the binding ability and selectivity towards G-quadruplex DNA in comparison with the previously reported 9-N-substituted berberine derivatives. Furthermore, qRT-PCR assay showed compound 3j led the down-regulation of c-myc gene transcription in leukemia cell line HL60, while little effect on normal cell line ECV-304, which was consistent with the behavior of an effective G-quadruplex ligand targeting c-myc oncogene.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Waihuan East Road 132, Guangzhou 510080, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.forename: Tian-Miao
authors.initials: TM
authors.lastname: Ou
authors.forename: Jia-Heng
authors.initials: JH
authors.lastname: Tan
authors.forename: Jin-Qiang
authors.initials: JQ
authors.lastname: Hou
authors.forename: Shi-Liang
authors.initials: SL
authors.lastname: Huang
authors.forename: Lian-Quan
authors.initials: LQ
authors.lastname: Gu
authors.forename: Zhi-Shu
authors.initials: ZS
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001599:Berberine / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D054856:G-Quadruplexes; D018922:HL-60 Cells; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors* / Q000235:genetics; D011804:Quinolines / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013237:Stereoisomerism; D013816:Thermodynamics; D014158:Transcription, Genetic / Q000187:drug effects* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D007546:Isoquinolines; D008024:Ligands; D016271:Proto-Oncogene Proteins c-myc; D011804:Quinolines; C559798:quinolino-benzo-(5, 6)-dihydroisoquindolium; D001599:Berberine; D004247:DNA; C037219:quinoline